PROJECT SUMMARY: Perinatal brain injury is a significant problem given the high incidence of prematurity in the United States, with an estimated increase of 28% over the past 20 years. It is now estimated that up to 40% of survivors of perinatal brain injury are compromised neurologically, including motor deficits, learning and behavioral problems. Our overall hypothesis is that magnetic resonance spectroscopy (MRS) may be a biomarker of the diffuse component of perinatal white matter injury and that altered neonatal NAA and NAA/myo-inositol ratio will correlate with long term neurodevelopmental outcome and thalamo-cortical abnormalities as assessed with advanced MR techniques at 6 years of age. We will specifically focus on premature infants at term equivalent age and term infants with congenital heart disease (transposition of the great arteries and single ventricle physiology). Our specific aims are: Aim 1: Determine "normative levels" of absolute concentration of NAA and myo-inositol in neonatal cerebral white matter using a longitudinal study design by (1a) performing MRS in term infants with no risk factors for perinatal white matter injury;(1b) performing longitudinal neurodevelopmental assessment at 18 months, 36 months and 6 years of age;(1c) performing DTI and VM MR imaging at 6 yrs of age. Aim 2: To determine the levels of absolute concentration of NAA and myo-inositol in the cerebral white matter using a longitudinal study design by (2a) performing MRS in term equivalent premature infants, (2b) performing longitudinal neurodevelopmental assessment at 18 months, 36 months and 6 years of age, and (2c) performing DTI and VM MR imaging at 6 yrs of age. Aim 3: To determine the levels of absolute concentration of NAA and myo-inositol in the cerebral white matter using a longitudinal study design by (3a) performing MRS in term infants with congenital heart disease (3b) performing longitudinal neurodevelopmental assessment at 18 months, 36 months and 6 years of age (3c) performing DTI and VM MR imaging at 6 yrs of age. As part of the career plan, the applicant will obtain skills in (1) advanced MR imaging techniques (2) clinical research outcome, advanced statistics and clinical management skills, and (3) neonatal neuropathology, pediatric neurology and pediatric neuro-psychology. RELEVANCE: This longitudinally designed study, using both advanced MR imaging and neurocognitive testing, will allow us to study the effects of perinatal white matter injury on long term neurodevelopmental function and thalamo-cortical structural plasticity in childhood. This project will help identify neonates with perinatal white matter injury at high risk for developing poor neurodevelopmental outcome for early intervention services.